Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Uniparental Disomy”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 829 records · Page 46Linked to original sources
PubMed1992

Beckwith-Wiedemann syndrome, tumourigenesis and imprinting.

The concurrent development of cytogenetic, clinical, genetic and molecular studies has led to the recognition that the different hereditary and non-hereditary forms of the Beckwith-Wiedemann syndrome and associated tumours result from an imbalance between maternal and paternal alleles. The most exciting development in the past year was the discovery of uniparental paternal disomy and the increased understanding, arising from studies in the mouse and in hereditary cases, of the role possibly played by imprinting and somatic mosaicism in partial and complete expression of this complex syndrome.

Alleles↗
PubMed2002

Genomic imprinting in fetal growth and development.

Each somatic cell of the human body contains 46 chromosomes consisting of two sets of 23; one inherited from each parent. These chromosomes can be categorised as 22 pairs of autosomes and two sex chromosomes; females are XX and males are XY. Similarly, at the molecular level, two copies of each autosomal gene exist; one copy derived from each parent. Until the mid-1980s, it was assumed that each copy of an autosome or gene was functionally equivalent, irrespective of which parent it was derived from. However, it is now clear from classical experiments in mice and from examples of human genetic disease that this is not the case. The functional activity of some genes or chromosomal regions is unequal, and dependent on whether they have been inherited maternally or paternally. This phenomenon is termed 'genomic imprinting' and the activity or silence of an imprinted gene or chromosomal region is set during gametogenesis. Genomic imprinting involving the autosomes appears to be restricted to eutherian mammals, and has most likely evolved as a result of the conflicting concerns of the parental genomes in the growth and development of their offspring. When the normal pattern of imprinting is disrupted, the phenotypes observed in humans and mice are generally associated with abnormal fetal growth, development and behaviour, illustrating its importance for a normal intrauterine environment. The characteristics of imprinted genes, their regulation and the phenotypes associated with altered imprinting are discussed.

Animals↗
PubMed2003

Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by features reminiscent of marked premature ageing. Here, we present evidence of mutations in lamin A (LMNA) as the cause of this disorder. The HGPS gene was initially localized to chromosome 1q by observing two cases of uniparental isodisomy of 1q-the inheritance of both copies of this material from one parent-and one case with a 6-megabase paternal interstitial deletion. Sequencing of LMNA, located in this interval and previously implicated in several other heritable disorders, revealed that 18 out of 20 classical cases of HGPS harboured an identical de novo (that is, newly arisen and not inherited) single-base substitution, G608G(GGC > GGT), within exon 11. One additional case was identified with a different substitution within the same codon. Both of these mutations result in activation of a cryptic splice site within exon 11, resulting in production of a protein product that deletes 50 amino acids near the carboxy terminus. Immunofluorescence of HGPS fibroblasts with antibodies directed against lamin A revealed that many cells show visible abnormalities of the nuclear membrane. The discovery of the molecular basis of this disease may shed light on the general phenomenon of human ageing.

Adult↗
PubMed1997

Imprinted expression of the murine Angelman syndrome gene, Ube3a, in hippocampal and Purkinje neurons.

Angelman syndrome (AS) is a human genetic disorder characterized by mental retardation, seizures, inappropriate laughter, abnormal galt, tremor and ataxia. There is strong genetic evidence that the disorder is associated with a maternally expressed, imprinted gene mapping to chromosome 15q11-13. Affected patients demonstrate varied molecular abnormalities, including large maternal deletions, uniparental paternal disomy (UPD). Imprinting mutations and loss of function mutations of E6-associated-protein (E6-AP) ubiquitin-protein ligase (UBE3A). All of these abnormalities are associated with loss of maternal expression of UBE3A. Although mutations in UBE3A cause AS, indicating that maternal-specific expression of UBE3A is essential for a normal phenotype, evidence for maternal-specific expression of UBE3A has been lacking. Using mice with partial paternal UPD encompassing Ube3a to differentiate maternal and paternal expression, we found by in situ hybridization that expression of Ube3a in Purkinje cells, hippocampal neurons and mitral cells of the olfactory bulb in UPD mice was markedly reduced compared to non-UPD littermates. In contrast, expression of Ube3a in other regions of the brain was only moderately or not at all reduced in UPD mice. The major phenotypic features of AS correlate with the loss of maternal-specific expression of Ube3a in hippocampus and cerebellum as revealed in the mouse model.

Angelman Syndrome↗
PubMed2001

Kinetic form discrimination in Prader-Willi syndrome.

Discrimination of the shape of motion-produced forms generated by random elements (i.e. second-order stimuli varying in element density and temporal correlation) was tested in four groups: (1) subjects with Prader-Willi syndrome (PWS), chromosome 15q deletion subtype; (2) subjects with PWS, uniparental maternal disomy (UPD) subtype; (3) equivalent non-PWS controls; and (4) normal controls. The performance of the normal controls exceeded that of all other groups (78% correct, P < 0.009). The PWS deletion (66%) and the equivalent control groups (59%) did not differ (P < 0.95). The UPD group performed significantly less well (38%, P < 0.04) than all the other groups. The performance of the PWS deletion and equivalent control groups is consistent with other data indicating that these populations encounter difficulty meeting the processing demands posed by second-order stimuli. The inferior performance of the UPD group may be attributed to receiving two active alleles of a maternally expressed gene influencing neural development. One candidate is the ubiquitin protein ligase gene (UBE3A), which is maternally expressed only and localized to the 15q region. Other possibilities include the requirement of a paternally expressed gene, residual mosaic trisomy 15 in the brain tissue or complex interactions including specific ratios of differentially spliced gene products.

Adult↗
PubMed2000

Interstitial 6q deletion with a Prader-Willi-like phenotype: a new case and review of the literature.

We report on an additional fourth case of Prader-Willi (PW)-like phenotype and an interstitial deletion of 6q. Despite sharing clinical characteristics, patients with a PW-like phenotype and a deletion of 6q, have features which distinguish them from Prader-Willi syndrome (PWS) patients. This case emphasizes the need to examine patients with suspected PWS, but who are negative for recognizable deletions of 15q11-q13 or uniparental maternal disomy of chromosome 15, for a deletion of 6q.

Child, Preschool↗
PubMed2001

Post-zygotic origin of complete maternal chromosome 7 isodisomy and consequent loss of placental PEG1/MEST expression.

Maternal UPD of chromosome 7 is associated with pre- and postnatal growth retardation (IUGR, PNGR) and Silver-Russell syndrome (SRS [MIM 180860]). We report a case of IUGR in a newborn with SRS stigmata. Using combined haplotyping and cytogenetic-FISH studies we characterized the lymphocytes, umbilical cord and four placental cotyledons. The results are consistent with complete maternal isodisomy 7 and trisomy 7 mosaicism of post-zygotic origin. The trisomic cell line was prevalent in trophoblast cells from two placental cotyledons. Trisomy 7 of post-zygotic origin is a frequent finding, but maternal isodisomy 7, due to trisomic rescue has never been reported. PEG1/MEST expression was evaluated on placenta cDNA and a specific transcript was revealed only in the cotyledons with a high percentage of trisomic cells and the presence of the paternal chromosome 7 contribution, but not in the placental biopsies with maternal isodisomy 7. The histological features of the four placental fragments revealed that isodisomy 7 correlates with a pattern of cotyledonary hyper-ramification due to an increase of the branching angiogenesis, which could be the result of a defect of angiogenesis caused by the absence of PEG1 product. The severe hypo-ramification of the two cotyledons, showing trisomy 7 mosaicism, may be due to the triplicate dosage of genes on chromosome 7. The delayed fetal growth could be the phenotypic effect of the imbalance between imprinted and non-imprinted genes on chromosome 7 in the fetus or the result of abnormal placental function during pregnancy.

Adult↗
PubMed2004

Identification and characterisation of imprinted genes in the mouse.

Imprinted genes are expressed specifically from one or other parental allele. Over 70 are now known, and about one-half of these are expressed from the paternal allele and one-half from the maternal allele. Most imprinted genes are clustered within imprinting regions of the mouse genome, regions which are associated with abnormal phenotypes when inherited uniparentally. Imprinted genes have been identified from surveys based on differential expression or differential methylation according to parental origin, as well as analyses of candidate genes, mutants and imprinted gene clusters. Many imprinted genes affect growth and development, and more than 25 per cent determine non-coding RNAs that may have a function in controlling imprinted gene expression.

Alleles↗
PubMed2002

Retinitis pigmentosa and allied diseases: numerous diseases, genes, and inheritance patterns.

Retinitis pigmentosa (RP) and allied diseases are heterogeneous clinically and genetically. Here we summarize the retinal cell types involved in these diseases, the large number of genes that cause them, and the variety of inheritance patterns that the affected families display. Special consideration is given to unusual inheritance patterns. The aggregate carrier frequency for recessive RP alleles may be as high as 10%.

Alleles↗
PubMed1994

Allelic methylation of H19 and IGF2 in the Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome with associated embryonal tumours. Most BWS cases are sporadic but familial cases occur in 15% of patients and in these there is linkage to chromosome 11p15. In addition, a small number of patients have cytogenetic abnormalities involving chromosome 11p15. Approximately 20% of sporadic BWS patients have uniparental paternal disomy (UPD) of chromosome 11p15. This finding together with the observation that penetrance in familial cases depends on parental transmission, suggests that the gene(s) for BWS are imprinted. The recent demonstration of biallelic expression of the otherwise maternally imprinted IGF2 gene in some BWS patients implicates excess IGF2 expression in the disease. Here we have analysed the allele-specific methylation patterns in the IGF2 gene and in the neighbouring and reciprocally imprinted H19 gene in a group of 42 BWS patients, 10 of which were mosaic UPD cases. We found that allelic methylation of both genes was normal in all non-UPD cases, with the paternal allele being methylated, and was increased in UPD cases in proportion with the disomic lineage. These findings suggest that sporadic BWS is not associated with a general alteration of methylation imprinting of the IGF2 and H19 genes. The methylation assay used in this study thus also offers a simple and reliable diagnostic test of UPD for 11p15.5. An unexpected finding was a distortion of the frequency of AvaII alleles at the IGF2 locus exclusively in UPD BWS cases (P < 0.001). This further implicates the IGF2 gene in aspects of the BWS phenotype.

Alleles↗
PubMed2006

Fetal growth restriction: the etiology.

Fetal growth restriction (FGR) is etiologically associated with various maternal, fetal and placental factors, although such an association may not be present in many cases. Maternal factors include hypertensive diseases, autoimmune disorders, certain medications, severe malnutrition, and maternal lifestyle including smoking, alcohol and cocaine use. Fetal etiologies include aneuploidy, malformations, syndromes related to abnormal genomic imprinting, perinatal viral or protozoan infections, preterm birth, and multiple gestation. Placental factors may involve many conditions including anatomical, vascular, chromosomal and morphological abnormalities. Better understanding of these etiologic conditions may lead to improved prediction, prevention and management of FGR.

Aneuploidy↗
PubMed2005

Advances in overgrowth syndromes: clinical classification to molecular delineation in Sotos syndrome and Beckwith-Wiedemann syndrome.

PURPOSE OF REVIEW: The clinical importance of overgrowth syndromes in the pediatric patient population has been increasingly recognized during the past decade, but clinical overlap among overgrowth syndromes often makes diagnostic categorization difficult. Advances in the molecular delineation of overgrowth syndromes in recent years have furthered our knowledge of the phenotypic spectrum of this group of conditions. This review focuses on developments in our understanding of the molecular mechanisms and phenotype-genotype correlations in the two most common overgrowth syndromes, Beckwith-Wiedemann syndrome and Sotos syndrome. The implications of these findings with respect to clinical diagnosis, medical management, and genetic counseling are discussed. RECENT FINDINGS: Recent reports have redefined the cardinal clinical features of Sotos syndrome, and the identification of two distinct types of molecular alterations in patients with this syndrome has enabled assessment of phenotype-genotype correlations. Recent studies in patients with Beckwith-Wiedemann syndrome have further expanded our understanding of the causative molecular mechanisms of this condition and provide evidence for specific genotype-phenotype correlations, most notably with respect to tumor risk. SUMMARY: Recognition of childhood overgrowth and investigation of diagnostic causes is important in anticipating appropriate medical management and facilitating the provision of genetic counseling. New developments in our understanding of the molecular basis and phenotypic expression of overgrowth syndromes provide additional tools in this often challenging process.

Beckwith-Wiedemann Syndrome↗